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Abstract:

Minimal residual disease (MRD), the post-treatment presence of a small submicroscopic amount of leukaemic cells in the bone marrow or other sites undetectable by conventional methods, has been recently shown to be one of the most important independent prognostic factors in childhood acute leukaemia. MRD can be detected by immunophenotyping by flow cytometry, PCR of chromosomal aberrations and PCR of clonal immunoglobulin or T-cell receptor (IG/TCR) rearrangements; each of these methods having certain advantages, disadvantages and limitations. In this study, which is a part of a larger MRD project, three different methods of MRD detection were first established, optimised, and validated according to the BIOMED-1 and Europe Against Cancer Program recommendations, and then used to monitor the MRD status of a group of 25 patients with childhood acute leukaemia (23 ALL, 2 AML) during at least 1-year follow-up. In 4 of the 23 ALL patients (17 %) MRD could be followed by only one method - half of them by FC, the other half by PCR of clonal IG/TCR rearrangements. Combined monitoring by FC and PCR (of chromosomal aberration or clonal IG/TCR rearrangements) was applicable in 7 patients (30 %) and all three approaches of MRD detection could be used in 5 patients (22 %). In the remaining 7 ALL patients enrolled in the study (30 %), MRD could not be monitored because either diagnostic of follow-up samples were missing. The 2 AML patients did not express any of the screened chromosomal aberrations and both were monitored by FC only.